Abstract
With an organ transplant, hematopoietic donor cells are transferred to the recipient. To study the relevance of the resulting microchimerism for allograft acceptance, we analyzed a rat model of cyclosporine-induced tolerance for strongly incompatible heart allografts. Using a monoclonal antibody that detects a donor-specific CD45 allotype (RT7a), we selectively depleted donor leukocytes at different times after transplantation (days 0 or 18). Depletion was similarly effective at both times. However, only depletion on day 0 prevented tolerance induction and was associated with severe acute or chronic graft rejection. This indicates that passenger leukocytes have an essential immunomodulatory effect on the induction phase of allograft acceptance.
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Acknowledgements
The authors thank L. Hänisch for animal care, M. Giesecke for microsurgical assistance and M.W. Hoffmann for critical review of the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft through Sonderforschungsbereich 265. S.K. was supported by a fellowship of the Alexander von Humboldt Stiftung; his present affiliation is First Department of Surgery, Nara Medical University, Kashihara, Nara 634, Japan.
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Ko, S., Deiwick, A., Jäger, M. et al. The functional relevance of passenger leukocytes and microchimerism for heart allograft acceptance in the rat. Nat Med 5, 1292–1297 (1999). https://doi.org/10.1038/15248
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DOI: https://doi.org/10.1038/15248
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